Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

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The purpose of this research study was to determine if an experimental drug called Aztreonam for Inhalation Solution (AZLI) was safe and effective to treat Burkholderia lung infections in patients with cystic fibrosis (CF).

Spirometry was used to assess pulmonary function, and the revised Cystic Fibrosis Questionnaire (CFQ-R) was used to assess quality of life. The CFQ-R is a validated, patient-reported outcome tool used to measure health-related quality of life for children and adults with CF.

The study consisted of a 24-week randomized phase, and a 24-week open-label phase. Primary and secondary efficacy analyses were conducted for the 24-week randomized phase only. Safety data were collected for both the randomized and open-label phases.

The relative change (AUCave) in FEV1 % predicted from baseline to Week 24 was analyzed. FEV1 % predicted is defined as FEV1 % of the patient divided by the average FEV1 % in the population for any person of similar age, sex and body composition. AUCave is the calculated area under the curve corrected for baseline and adjusted by the number of days on study through Week 24.

Secondary Outcome Measures
:

Total Number of Systemic and/or Inhaled Antibiotic Courses for Respiratory Events [ Time Frame: Baseline to Week 24 ]

The total number of systemic and/or inhaled antibiotic courses for respiratory events from baseline to Week 24 was analyzed. A single antibiotic course may represent the use of multiple antibiotics.

AUCave of Change in CFQ-R RSS Scores From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]

The change (AUCave) in CFQ-R RSS scores from baseline to Week 24 was analyzed.

The range of scores (units) within the RSS domain is 0 to 100 with higher scores indicating fewer symptoms.

AUCave of Relative Change From Baseline to Week 24 in FEV1 [ Time Frame: Baseline to Week 24 ]

The relative change (AUCave) from baseline to Week 24 in mean (SE) FEV1 was analyzed. FEV1 is defined as the maximal volume of air that can be exhaled in 1 second.

AUCave of Relative Change From Baseline to Week 24 in FVC [ Time Frame: Baseline to Week 24 ]

The relative change (AUCave) from baseline to Week 24 in mean (SE) FVC was analyzed. FVC is defined as the volume of air that can forcibly be blown out after taking a full breath.

AUCave of Relative Change From Baseline to Week 24 in FEF25-75 [ Time Frame: Baseline to Week 24 ]

The relative change (AUCave) from baseline to Week 24 in mean (SE) FEF25-75 was analyzed. FEF25-75 is defined as the forced expiratory flow from 25% to 75% of the FVC.

AUCave of the Change From Baseline to Week 24 in Physical Functioning Score as Assessed by the CFQ-R [ Time Frame: Baseline to Week 24 ]

The change (AUCave) from baseline to Week 24 in the physical functioning score as assessed by the CFQ-R was analyzed.

The range of scores (units) in the CFQ-R physical functioning domain is 0 to 100 with higher scores indicating better QOL.

AUCave of the Change From Baseline to Week 24 in Weight Score as Assessed by the CFQ-R [ Time Frame: Baseline to Week 24 ]

The change (AUCave) from baseline to Week 24 in the weight score as assessed by the CFQ-R was analyzed.

The range of scores (units) in the CFQ-R weight domain is 0 to 100 with higher scores indicating better QOL.

AUCave of the Change From Baseline to Week 24 in Treatment Burden Score as Assessed by the CFQ-R [ Time Frame: Baseline to Week 24 ]

The change (AUCave) from baseline to Week 24 in the treatment burden score as assessed by the CFQ-R was analyzed.

The range of scores (units) in the CFQ-R treatment burden domain is 0 to 100 with higher scores indicating better QOL.

Change in BMI From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]

The change in BMI from baseline to Week 24 was analyzed.

Change in Burkholderia Spp. CFU in Sputum From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]

The change in Burkholderia spp. CFU in sputum from baseline to Week 24 was analyzed.

Percentage of Days Participants Used Antibiotics [ Time Frame: Baseline to Week 24 ]

The percentage of days participants used antibiotics from baseline to Week 24 was analyzed. Antibiotics ongoing at baseline or started on or after first dose date were included in the analysis. A single antibiotic course could represent the use of multiple antibiotics. Days of antibiotic use included unique days.

Percent of Days Hospitalized [ Time Frame: Baseline to Week 24 ]

The percentage of days hospitalized from baseline to Week 24 was analyzed.

Percentage of Missed School or Work Days [ Time Frame: Baseline to Week 24 ]

The percentage of days participants missed school or work from baseline to Week 24 was analyzed.

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At least one positive sputum (or bronchoalveolar lavage) culture (obtained at any point in time) confirmed to be Burkholderia spp. by the Cystic Fibrosis Foundation (CFF) Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory).

Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment were eligible, but must have been at least 1 week into their off-treatment cycle at the time of baseline assessment. Subjects receiving continuous aerosolized antibiotic treatment were eligible without restriction on their aerosolized antibiotic treatment.

Subjects (and parent/guardian as required) must have been able to provide written informed consent/assent prior to any study-related procedures,

Ability to perform reproducible pulmonary function tests

Sexually active females of childbearing potential must have agreed to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug. A highly effective method of birth control was defined as a method that would result in a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner.

Exclusion Criteria:

Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)

Administration of AZLI treatment within the 28 days prior to randomization/baseline